Over 16 million people in the U.S. suffer from severe joint pain and related dysfunction, such as loss of motion, as a result of injury or osteoarthritis. In particular, loss of function of the knees and other joints can severely impact mobility and thus the patient's quality of life. The biological basis of joint problems is the deterioration of articular cartilage, which covers the bone at the joint surface and performs many complex functions. The deterioration of anticular cartilage is often preceded by the delamination of the cartilage. Medical intervention at the delamination stage of the disease provides an opportunity to circumvent further degradation and associated complications.
The interface between bone and cartilage is the interface between a vascularized (the bone) and mostly avascular (the cartilage) tissue as well as mineralized (ossified) and nonminerilized collagen matrices. Traumatic injury, as well as such conditions as osteoarthritis and aging, often results in damage to the articular cartilage, which may also involve damage to the underlying bone. Often, this damage manifests itself in the delamination of the cartilage from the bone. Therefore, there is a need for a method of treatment which meets the disparate needs of both tissue types and allows or encourages the healing process to progress towards restoration of both types of tissues at the same site by promoting the reattachment or relamination of the cartilage to the bone.
Prior art methods for promoting the reattachment of cartilage to the bone are not without problems. Prior art treatments include, for example, autograph procedures such as osteochondral autograph transfer system (Mosaicplasty). These procedures remove an osteochondral plug from a non-load bearing area and graft it into the defect site. However, these procedures require invasive surgical procedures and, therefore, longer recuperative times.
Arthroscopic lavage is a “cleaning up” procedure of the knee joint. This short term solution is not considered an articular cartilage repair procedure but rather a treatment to reduce pain, mechanical restriction and inflammation. Lavage focuses on removing degenerative articular cartilage flaps and fibrous tissue. The main target group is patients with very small defects of the articular cartilage. Arthroscopic debridement is a surgical technique that is effective in removing areas of loose, mechanically redundant cartilage (joint lining) and inflamed tissue (synovitis) from the joint.
Other procedures consist of injecting cartilage cells under a periosteal flap, however, the procedure lacks inter-patient consistency with some patients maintaining little relief months or years later and the surgical procedure is technically challenging and expensive. Marrow stimulating techniques including abrasion arthroscopy, subchondral bone drilling and microfracture typically result in fibrocartilage filling the defect site. In these procedures, the subchondral bone is perforated to generate a blood clot within the defect. However, marrow stimulation techniques often insufficiently fill the chondral defect and the repair material is often fibrocartilage (which is not as good mechanically as hyaline cartilage). The blood clot takes about 8 weeks to become fibrous tissue and it takes 4 months to become fibrocartilage thus needing extensive rehabilitation time. However, there is a significant possibility of the symptoms returning as the fibrocartilage wears away, forcing the patient to undergo further articular cartilage repair.
Marrow stimulation techniques have been augmented with administration of peripheral blood monocytes (PMBCs) with limited success. Microdrilling surgery creates a blood clot scaffold on which injected PBPC's can be recruited and enhance chondrogenesis at the site of the contained lesion (Saw, K Y, et al., (Epub 2011 Feb. 19). “Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic Acid after arthroscopic subchondral drilling: a report of 5 cases with histology”. Arthroscopy 27 (4):493).
Allogenic transplantation of osteochondral grafts has had clinical success, but supply is limited and has a risk of infection. This technique/repair requires transplant sections of bone and cartilage. The damaged section of bone and cartilage is removed from the joint then a new healthy dowel of bone with its cartilage covering is punched out of the same joint and replanted into the hole left from removing the old damaged bone and cartilage. The healthy bone and cartilage are taken from areas of low stress in the joint so as to prevent weakening the joint. Depending on the severity and overall size of the damage multiple plugs or dowels may be required to adequately repair the joint, which becomes difficult for osteochondral autografts and can limit its use to non-severely damaged tissue.
The prior art techniques involving removal of the delaminated cartilage is actually not in the patient's best interest because, as described above, the tissue that forms to replace the removed cartilage, called fibrocartilage, is not as robust as the original hyaline cartilage.
Other prior art techniques include the use of scaffolds or matrixes to provide a structure upon which chondrocytes may migrate and form new cartilage. For example, one such technique is provided in US Patent Application No. 2003/0114936, which describes implantable composite materials of gradated matrices for the promotion of cell growth, which is incorporated herein by reference. Other prior art references directed towards the use of scaffolds and matrices are described, infra.
Thus, because of the limitations of the prior art procedures, it has been recognized that reattachment of the hyaline cartilage is desirable. The hyaline cartilage does not readily reattach on its own—if it did treatment options would not be necessary. Prior art attempts have used adhesives, for example. However, these attempts have met with limited success. This is at least in part because even so called “biocompatible” adhesives are made from materials foreign to the patient and/or the joint. Thus, breakdown of the adhesion frequently occurs thereby only providing a temporary solution to the condition. Further, the adhesive layer creates a barrier to the cartilage cells that are necessary for reattachment of the cartilage to the underlying bone.
Thus, what is needed in the art are new compositions and procedures that provide for the successful reattachment of delaminated hyaline cartilage preferably without surgical intervention or with minimal surgical intervention.